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The VACS Index Predicts Mortality in a Young, Healthy HIV Population Starting Highly Active Antiretroviral Therapy

Bebu, Ionut PhD*; Tate, Janet ScD; Rimland, David MD; Mesner, Octavio MS*; Macalino, Grace E. PhD*; Ganesan, Anuradha MD*,§; Okulicz, Jason F. MD*,‖; Bavaro, Mary MD*,¶; Weintrob, Amy C. MD*,§; Justice, Amy C. MD, PhD; Agan, Brian K. MD*for the Infectious Disease Clinical Research Program HIV Working Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2014 - Volume 65 - Issue 2 - p 226–230
doi: 10.1097/QAI.0000000000000045
Epidemiology and Prevention

Background: The Veterans Aging Cohort Study (VACS) index is a weighted combination of age and 8 clinical variables. It has been well correlated with all-cause mortality among HIV-infected patients. The US Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed; so, evaluation of the VACS index in this population is of great interest.

Methods: NHS subjects have medical history and laboratory data collected at 6-month visits. We performed an external validation of the VACS index in the NHS evaluating correlation, discrimination, and calibration for all-cause mortality after highly active antiretroviral therapy initiation (HI). We then tested whether combining longitudinal VACS index values at different time points improves prediction of mortality.

Results: The VACS index at 1 year after HI was well correlated with all-cause mortality (Harrell c statistic 0.78), provided good discrimination (log-rank P < 0.05), and was marginally well calibrated using Brier score. Accounting for VACS index at HI and 6 months after HI significantly improved a standard model, including only the VACS index at 1 year after HI (net reclassification improvement = 25.2%, 95% CI: 10.9% to 48.9%).

Conclusions: The VACS index was well correlated and provided good discrimination with respect to all-cause mortality among highly active antiretroviral therapy initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration that could improve fit among similar patients. Considering VACS index at HI and 6 months improved outcome prediction and allowed earlier risk assessment.

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*Department of Preventive Medicine and Biometrics, Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD;

Yale University School of Medicine and the Veterans Affairs Healthcare Systems, West Haven, CT;

Veterans Affairs Medical Center and Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA;

§Division of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, MD;

Division of Infectious Diseases, San Antonio Military Medical Center, TX; and

Division of Infectious Diseases, Naval Medical Center San Diego, CA.

Correspondence to: Ionut Bebu, PhD, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814 (e-mail:

All authors contributed to the content of the manuscript and concurred with the decision to submit it for publication.

Supported by Infectious Disease Clinical Research Program (IDCRP-000), a Department of Defense program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

The content of this publication is the sole responsibility of the authors and does not necessarily reflect the views or policies of the National Institutes of Health or the Department of Health and Human Services, the Department of Veterans Affairs, the Department of Defense, or the Departments of the Army, Navy, or Air Force or Veterans Affairs. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government.

Received October 24, 2013

Accepted October 24, 2013

© 2014 by Lippincott Williams & Wilkins